CN103813830B

CN103813830B - Therapeutic micro-electric current delivery apparatus and method thereof

Info

Publication number: CN103813830B
Application number: CN201280045446.5A
Authority: CN
Inventors: A·F·多尔; J·M·格伦德; P·D·霍克; M·克卢考斯卡; D·S·萨鲁姆; D·J·小怀特; S·钦纳帕雷迪
Original assignee: Braun GmbH
Current assignee: Braun GmbH
Priority date: 2011-09-20
Filing date: 2012-09-14
Publication date: 2016-08-24
Anticipated expiration: 2032-09-14
Also published as: WO2013043769A1; US20130071805A1; US20130071807A1; CN103813830A; JP2014526343A; JP5847946B2; US20130072851A1; KR101633564B1; US20130071806A1; EP2758124B1; CA2849243A1; WO2013043771A1; EP2758121A1; CN103796712B; KR101633565B1; CA2849457A1; EP2758124A1; EP2758123A1; CN103796711B; WO2013043770A1

Abstract

A kind of therapeutic micro-electric current delivery apparatus, it is included in the first electrode of the first user position and user's electrical contact；The second electrode in the second user position with user's electrical contact；Power supply, it is operable to provide the first electromotive force at the first electrode and provides the second electromotive force at the second electrode；With micro-current control circuit, itself and the first electrode, the second electrode and power supply electric connection.The electrical contact of the electrical contact of the first electrode of the first user position and the second electrode of the second user position realizes circuit.Micro-current control circuit produces between the first position and the second position by micro-electric current I of user_{Rank liter}, described micro-electric current is at rise time t_RiseInterior from initial current I_InitialIncrease to terminal electric current I_Terminal.Invention also discloses oral care appliance and micro-current control method.

Description

Therapeutic micro-electric current delivery apparatus and method thereof

Technical field

Present patent application relates generally to Iontophoretic device, more specifically, present patent application relates to And therapeutic micro-electric current delivery apparatus, oral care appliance and provide micro-electric current of increase to pass to patient The method of the amount of sending.

Background technology

Ionotherapy is that one utilizes small area analysis (or electric charge) to carry out the dermal delivery through patient Medicine or the medical technology of chemicals.Iontophoretic application is quite varied, and can be used to control Treat many illness such as arthritis, wart, bleb and other illnesss many.Recently, ionotherapy It is used for oral care appliance such as toothbrush to help to remove dental plaque and increase from the tooth of user Delivery to the fluorine anion of tooth.The typical oral care appliance delivering the micro-electric current of ion is limited In 80 μ A, because it is unpleasant to have shown that the levels of current more than 80 μ A causes user to produce Sensation, such as pain, electrical sensation and/or tart flavour.But, experimental data is pointed out, less than 80 μ A's Gas current level provides only minimum in the iontophoretic application of MC or does not provide and control The property treated beneficial effect.It may also be desired that outside Iontophoretic device and MC are applied be System increases gas current level to increase such device and effect of system.

Therefore, it is desirable to alternative therapeutic micro-electric current delivery apparatus, oral care appliance and Method, they make it possible to increase the micro-levels of current of ion and be not resulted in the use of such device and method Person produces unpleasant sensation.

Summary of the invention

In one embodiment, a kind of therapeutic micro-electric current delivery apparatus includes the first electrode, its energy Enough operations are to make electrical contact with user in the first user position；Second electrode, its be operable to Make electrical contact with user with in the second user position；Power supply, it is operable to at the first electrode Place provides the first electromotive force and provides the second electromotive force at the second electrode；With micro-current control circuit, its with First electrode, the second electrode and power supply electric connection.The electricity of the first electrode of the first user position connects The electrical contact of tactile the second electrode with the second user position is real between the first electrode and the second electrode Existing circuit.When completing circuit, micro-current control circuit produces and makes in the first user position and second By micro-electric current I of user between user position_{Rank liter}, described micro-electric current is at rise time t_RiseIn from Initial current I_InitialIncrease to terminal electric current I_Terminal。

In another embodiment, a kind of oral care appliance includes handle portions；It is connected to shank The brushhead portion of part, brushhead portion includes brush filament；Second electrode, its be positioned in handle portions and It is operable to make electrical contact with user in the first user position；With the first electrode, it is positioned at brush In head part and be operable to in the electrical contact of the oral cavity of the second user position and user.Should Oral care appliance also includes power supply, its be operable to provide at the first electrode the first electromotive force and Second electromotive force is provided at the second electrode；With micro-current control circuit, itself and the first electrode, the second electrode With power supply electric connection.The electrical contact of the first electrode of the first user position and the second user position The electrical contact of second electrode at place realizes circuit between the first electrode and the second electrode.Complete circuit Time, micro-current control circuit produces between the first user position and the second user position by making Micro-electric current of user, this micro-electric current has the maximum more than 100 μ A.

In another embodiment, a kind of method of micro-electric current of oral administration therapeutic to user Including: providing oral care appliance, it has the second electrode and in handle portions in brushhead portion There is the first electrode；There is provided power supply, its be operable to produce at the first electrode the first electromotive force and The second electromotive force is produced at second electrode.Send out between the first electrode and the first user position of user When life electrically connects and electrical connection simultaneously occurs between the second electrode and the oral cavity of user, the party Method also includes producing between the first user position and oral cavity by micro-electric current I of user_{Rank liter}, institute State micro-electric current at rise time t_RiseInterior from initial current I_InitialIncrease to terminal electric current I_Terminal。

Accompanying drawing explanation

Should be appreciated that aforementioned general remark and further detail below all describe various embodiment, And aim to provide general introduction or framework for character and the spy understanding claimed subject matter Property.Described various embodiments are further understood from by accompanying drawing to provide, and they are incorporated into this In specification and constitute the part of this specification.The figures illustrate various enforcement as herein described Example, and it is used for explaining principle and the behaviour of claimed subject matter together with this specification Make.

Fig. 1 schematically depict controlling according to one or more embodiments shown and described herein The electric assembly of the micro-electric current delivery apparatus of the property treated；

Fig. 2 schematically depict according to the one or more embodiments being illustrated and described herein Therapeutic micro-electric current delivery apparatus；

Fig. 3 schematically depict according to the one or more embodiments being illustrated and described herein Power circuit and micro-current control circuit；

Fig. 4 A-4E schematically depict according to the one or more realities being illustrated and described herein Execute the oral care implement of therapeutic micro-electric current delivery apparatus of example；

Fig. 4 F schematically depict according to the one or more embodiments being illustrated and described herein The iontophoresis device of therapeutic micro-electric current delivery apparatus；

Fig. 5 A depicts to graphically according to the one or more enforcements being illustrated and described herein The direct current rank of example rise micro-current methods；

Fig. 5 B depicts to graphically according to the one or more enforcements being illustrated and described herein The alternating current rank of example rise micro-current methods；

Fig. 5 C depicts to graphically according to the one or more enforcements being illustrated and described herein The alternating current rank of example rise micro-current methods；

Fig. 5 D depicts to graphically according to the one or more enforcements being illustrated and described herein The alternating current rank of switching between positive current and negative current of example rise micro-current methods；

Fig. 5 E depicts to graphically according to the one or more enforcements being illustrated and described herein The alternating current rank of switching between positive current and negative current of example rise micro-current methods；

Fig. 6 A depicts the following two kinds micro-electric current experiment electricity in the oral cavity of user to graphically Comparison between pressure drop: the micro-electric current of anode that non-rank rise and the rank with 100% operation dutycycle rise The micro-electric current of anode；

Fig. 6 B depicts the following two kinds micro-electric current experiment electricity in the oral cavity of user to graphically Comparison between pressure drop: the micro-electric current of anode that non-rank rise and the rank with 50% operation dutycycle rise The micro-electric current of anode；

Fig. 6 C depicts the following two kinds micro-electric current experiment electricity in the oral cavity of user to graphically Comparison between pressure drop: the micro-electric current of negative electrode that non-rank rise and the rank with 100% operation dutycycle rise The micro-electric current of negative electrode；

Fig. 6 D depicts the following two kinds micro-electric current experiment electricity in the oral cavity of user to graphically Comparison between pressure drop: the micro-electric current of negative electrode that non-rank rise and the rank with 50% operation dutycycle rise The micro-electric current of negative electrode；And

Fig. 7 is chart, during micro-electric current that its non-rank depicting applying 80 μ A to graphically rise The result of comparative study.

The VSC halitosis instrument result of the 5th day of Fig. 8 display comparison research-oral malodor.

The tongue sample GNA bacterium result of the 5th day of Fig. 9 display comparison research-oral malodor.

Detailed description of the invention

The micro-electric current of therapeutic that presently disclosed embodiment relates generally to the micro-electric current of patient delivery is passed Send apparatus and method.Such as, this type of therapeutic micro-electric current delivery apparatus and method can be used for iontophoresis The application of therapy, wherein applies micro-electric current to patient and controls to deliver medicine, material, reagent or generation Therapeutic effect.In general, presently disclosed embodiment makes to be applied to user's (or patient) Micro-levels of current can increase, and do not allow user experience generally may be with micro-electric current of this level Relevant unpleasant sensation.More specifically, embodiment as herein described make use of the electric current that rank rise Controlling, described electric current controls to make the level of micro-electric current increase to terminal from initial current within certain period Electric current.

Embodiment can be implemented as having the first electrode and the device of the second electrode, described first electrode Kept by user or in other words make electrical contact with certain region of user's health, and described second Electrode is intended to be applied to the region (such as, the oral cavity of user) relevant to ionophoresis.Micro-electric current The health of user is flow through between the region of the first electrode and the health of the second electrode contact, because The health of user realizes circuit between the first electrode and the second electrode.The electric current that described rank rise controls Effect be to limit the sensation experienced of user.Such as, in MC is applied, described rank The electric current risen controls to reduce intraoral voltage drop.Therapeutic micro-electric current is described in detail below pass Send the various embodiments of apparatus and method.

Although these embodiments are herein defined as combining oral care appliance such as electric toothbrush or scraping tongue Device describes, but embodiment is not limited to these.Presently disclosed embodiment can be used for various respectively The iontophoretic application of sample, such as using sulphur glycosides when treating bleb, in treatment oral cavity Use methylprednisolone sodium succinate during ulcer, use copper sulphate when treating tinea pedis, at treatment wart Time use salicylate, use antiinflammatory medicine, diagnose cystic fibrosis, treat various skin disease, Cosmetic applications and other application many.

Referring now to Fig. 1, it is shown that the group of an embodiment of therapeutic micro-electric current delivery apparatus 100 The general synoptic diagram of some in part.Therapeutic micro-electric current delivery apparatus 100 generally comprises power supply 102, micro-current control circuit the 104, first electrode 106 and the second electrode 108.Power supply 102 can be Following any power supply, it can produce according to the application-specific implementing therapeutic micro-electric current delivery apparatus 100 Raw micro-electric current (ion).The most such as, in the application of oral care appliance, power supply 102 batteries that can include micro-electric current that scope can be provided to be 50 to 1000 μ A.Power supply 102 also may be used For AC-DC converter circuit, DC-DC voltage regulator circuit or any suitable circuit with obtain from Voltage levvl and micro-levels of current specific to the application of sub-electric osmose therapy.The most such as, exist In MC application, the electromotive force that power supply 102 can produce about 30 volts is iontophoretic to increase Effect also overcomes the high resistance of the electrically human body parts of (ion) circuit.

First electrode and the second electrode 106,108 are such as bottom electrode, and they are configured to and user One or more positions electrical contact of health.Therefore, the first electrode and the second electrode 106,108 should For conduction.In one embodiment, the first electrode and the second electrode 106,108 are by metal material system Become.In another embodiment, the first electrode and/or the second electrode 106,108 can be to touch electricity Pole, they nonmetallic materials including being filled with carbon filler, such as entitled " Oral Care Device " U.S. Patent application 12/014, (such as, be dispersed in nonconductive resin such as ABC tree described in 487 Carbon fiber in fat).Although it should be pointed out that, the first electrode be shown as with negative polarity (-) Be associated, and second electrode be illustrated for positive polarity (+) be associated, but embodiment It is not limited to this.First electrode can be associated with positive polarity, and the second electrode can be relevant to negative polarity Connection.

Micro-current control circuit 104 is following circuit, its can by the health of user with institute Desired micro-levels of current completes to provide gas current during circuit.It addition, micro-current control circuit 104 Also realize the sense controlling to be experienced that the rank to the micro-electric current being applied to user rise with restriction user Feel.Such as, Fig. 5 A-5C depicts the exemplary micro-electric current that can be produced by current control circuit 104 Control method.This slightly current control method and current control circuit is described in more detail 104。

Fig. 2 depicts the figure of the therapeutic micro-electric current delivery apparatus being implemented as oral care appliance 120 Shape illustration.Should be appreciated that the module arrangement of oral care appliance 120 is merely illustrative, and real Execute example and be not limited to this type of module arrangement or the configuration arrangement of shown oral care appliance 120.Oral cavity Care device 120 includes main body cover 121 and oral care implement 126.Main body cover 121 limits Handle portions on the first end of oral care appliance 120.Oral care implement 126 is connected to main Body case 121 thus limit the second end of oral care appliance 120.In one embodiment, mouth Chamber care implement 126 is removably coupled to main body cover 121 so that have the oral cavity of phase heterogeneous Care implement could attach to main body cover 121 (such as, tongue scraper or dental floss tooth-cleaning instrument).One In individual alternative embodiment, oral care implement 126 can not remove from main body cover 121, Making main body cover 121 and oral care implement 126 is a black box.Main body cover 121 can It is made from a material that be electrically non-conductive, the plastics such as molded.

Shown oral care implement 126 generally comprises bar part 128 and brushhead portion 129, institute State the electric toothbrush head that brushhead portion is configured to have toothbrush bristle 127 associated there.Bar Part 128 and brushhead portion 129 all can be made from a material that be electrically non-conductive, such as plastic material.Oral cavity is protected Science and engineering tool 126 has the first electrode 106 that can include one or more conductive region.Shown In embodiment, the first electrode 106 includes that conductive pad, described conductive pad are positioned at opening of brushhead portion 129 In mouthful so that the conductive pad of the first electrode 106 is exposed to during the operation of oral care appliance 120 The oral cavity of user.

As in figure 2 it is shown, the second electrode 108 is arranged in main body cover 121 so that when user grabs When holding main body cover 121 with operation oral care appliance 120, it can contact with the torch of user.As Upper described, the second electrode 108 can be by metal material, the non-conductive tree that is wherein dispersed with conductive carbon fibre Fat or any other conductive material are made.Should be appreciated that embodiment is not limited to shown in Fig. 2 second The configuration of electrode.In one embodiment, it is provided that optional oscillation actuator 122, and joined Receive power supply 102.Oscillation actuator 122 is configurable to high frequency wobbles to provide MC The vibration of device 120.Main body cover 121 may also comprise other assemblies, such as on/off button or open Pass, mode selecting button or switch etc..

The various electricity assemblies for producing the micro-electric current of therapeutic ion being maintained in main body cover 121. Power supply 102 (that is, battery) positions in the enclosure, and wherein the first polarity of power supply 102 is (such as, Positive polarity) it is electrically coupled to the second electrode 108.Relative polarity (such as, the negative pole of power supply 102 Property) by micro-current control circuit 104 and the first electrode 106 electricity phase in oral care implement 126 Close.Equally, depend on application-specific, the pole being associated with the first electrode and the second electrode 106,108 Property can be converse.

Micro-current control circuit 104 may be installed other knots in printed circuit board (PCB) or main body cover 121 On structure.As in figure 2 it is shown, micro-current control circuit 104 can include pulse generation circuit 123 and pulse Drive circuit 124.Pulse generation circuit 123 and pulse driving circuit 124 are illustrated at two things The circuit separated in reason, it is to be understood that, in certain embodiments, said two circuit can be implemented For single circuit.Pulse generation circuit 123 can generate expectation and be applied to the waveform of user, and arteries and veins Rush drive circuit 124 can amplify described waveform with have for specific ion electric osmose therapy application suitable Current value.Example waveform is pictured in Fig. 5 A-5C.

It should be pointed out that, in some iontophoretic application, with the micro-electricity producing rank liter The electronic device that stream is associated can be not kept in the shell of therapeutic micro-electric current delivery apparatus 100, and Being held in the hood separated, described hood is electrically coupled to the micro-electric current of therapeutic kept by user Delivery apparatus 100.

Electrically (ion) circuit is by following offer: the negative polarity of power supply 102 and micro-electric current control electricity Electrical connection between road 104, electrical connection between micro-current control circuit 104 and the first electrode 106 Electrical connection between (shown in dotted line 125a), the positive polarity of power supply 102 and the second electrode 108 Conductive path between (shown in dotted line 125b) and the hand of user and oral cavity is (by dotted line Shown in 150).When user grasps the first electrode 106 of oral care appliance 120 and by brush 126 and first electrode 106 when being placed in its oral cavity, it is the formation of described circuit.When user from When brush 126 and the first electrode 106 are taken out in its oral cavity, just it is disconnected described circuit.More generally Say, when user grasps the second electrode 108 of therapeutic micro-electric current delivery apparatus 100 and will treat First electrode 106 of the micro-electric current delivery apparatus 100 of property is applied to (example during certain region of its skin As, it is applied on pin remove sole wart using salicylate by ionotherapy) time, just Define described circuit.

Referring now to Fig. 3, depict the micro-current control circuit 104 according to an embodiment and power supply The schematic diagram of 102.Should be appreciated that and can use other circuit or the correction form to circuit shown in Fig. 3 Produce the micro-current waveform of ion that Fig. 5 A-5C is painted, and embodiment is not limited to the signal of Fig. 3 Property embodiment.The power supply 102 of shown embodiment includes battery 101 and voltage-stablizer 103.Voltage stabilizing Device 103 receives the voltage of battery 101 and provides ground reference current potential 109, relative to ground reference current potential Positive rail current potential 105 (V+) (such as ,+30V) and negative relative to ground reference current potential Power rail 107 (V-) (such as ,-30V).Should be appreciated that and can utilize other electromotive forces.Just provide Power rail current potential 105 and negative power rail current potential 107 are to apply male or female polarity.By voltage-stablizer 103 voltages provided can be depending on the application of specific ion electric osmose therapy and change.Fig. 3 is painted (such as, brush teeth, gums cleans and scrapes for MC application for circuit and described voltage Tongue).

Micro-current control circuit 104 generally comprises pulse generation circuit 123 and pulse driving circuit 124.Micro-current control circuit 104 can be following any circuit, and it can be with CF, duty Ratio, levels of current etc. produce the electric current that rank rise and control waveform (such as, that shown in Fig. 5 A-5C A bit).

In one embodiment, pulse generation circuit 123 includes microcontroller 112 and conversion Device circuit or chip 113 (DAC), they cooperations are to produce controlling corresponding to user to be applied to The waveform of the micro-electric current of the property treated.The waveform produced by pulse generation circuit 123 is by pulse driving circuit 124 Amplify, therefore can have the voltage less than the voltage produced needed for desired micro-electric current.Such as, ripple The voltage of shape pulse can be between the logic voltage level between zero-sum microcontroller in the range of.Micro-control Device 112 processed can provide instructions to D-A converter 113 to produce the pulse being constituted described waveform.Institute State waveform to produce by the mode of shown pulse generation circuit 123.Such as, these waveforms Can be produced by the computer with D-A converter card, or be produced by such as forcing function generator.

There is provided as it has been described above, pulse driving circuit 124 is configured to amplify by pulse generation circuit 123 Waveform so that desired micro-levels of current (and desired frequency and dutycycle) is applied in To user.Pulse driving circuit 124 includes operational amplifier 116, and described operational amplifier receives As the waveform pulse string provided by pulse generation circuit 123 of input, and produce as output The micro-electric current of therapeutic.Therefore, operational amplifier 116 is used as the current source of waveform amplification train of pulse.Fortune Calculate amplifier 116 and be electrically connected to positive rail and the negative power rail of power supply 102, and be electrically coupled to electricity Stream sense resistor 111, described current-sense resistor is further coupled to ground reference current potential.Computing The output of amplifier 116 is electrically coupled to the first electrode 106, and described first electrode fills at MC The situation put is intended to be positioned in the oral cavity of user.Second electrode 108 passes through current sensing resistor Device is electrically coupled to ground reference current potential.

There is provided current-sense resistor 111 with provide the micro-electric current of ion feedback, described in fed back through User reaches microcontroller 112 and is supplied to micro-levels of current of user with monitoring regulation.One In individual embodiment, current-sense resistor 111 is 1k Ω resistor so that current-sense resistor The 1mV at 111 two ends corresponds to 1 μ A.

In the embodiment shown in fig. 3, pulse generation circuit 123 and pulse driving circuit 124 can be by Overvoltage protection is protected.Zener diode 117 and 118 would span across the voltage of user and limits For less than user's overvoltage value, such as 30V.Zener diode 114 and 115 is by limiting voltage It is made as less than pulse generation circuit overvoltage such as 10V to protect D-A converter 113 and microcontroller Device 112.

In the situation of MC, it is contemplated that using of gas current can be used to help from tooth and tooth Gum is removed dental plaque and uses fluorine ion via iontophoresis normal direction tooth.Passed by the micro-electric current of therapeutic The micro-electric current of ion sending device 100 to provide can flow to oral cavity from brush 126 by the saliva of user and glue Liquid and/or tooth, enter into across health in the hand of user, and returns to the micro-electric current of therapeutic In the shank of delivery apparatus 100.

Fig. 4 A-4E shows oral care implement and the various embodiments of the first electrode 106.Oral cavity Care implement and the first electrode can use various configuration.Should be appreciated that embodiment is not limited to figure Those configurations that 4A-4F is drawn.Seeing Fig. 4 A, brush 126 ' is plotted has the first electrode, Described first electrode includes the first conductive pad 106a of neighbouring brush filament 127 location and is positioned at brush filament The second conductive pad 106b below 127.Therefore the brush 126 ' that Fig. 4 A is painted provides and is available for ion Two positions that electric current flows through.The brush 126 that Fig. 4 B is painted has and is positioned at below brush filament 127 Single conductive pad 106, and the brush 126 that Fig. 4 C is painted " have the single of neighbouring brush filament 127 location Conductive pad 106 ".It is also contemplated that brush filament 127 self is conducted electricity and is used as the first electrode.

Fig. 4 D and 4E shows a kind of below embodiment, and wherein the first electrode is in being positioned at brush filament One or more insulated conductors 106 between 127 " ' form.Fig. 4 E shows shown in Fig. 4 D exhausted Edge wire 106 " ' the close-up view of an embodiment.Insulated conductor 106 " ' include by any conduction Conductor wire core 130 that the most pliable and the toughest metal material of material is made and around outside conductor wire core 130 Insulation sleeve 132.External insulation sleeve 132 is by the most pliable and the toughest non-conducting material system for toothbrush application Become.A part for conductor wire core 130 extends beyond external insulation sleeve 132 so that it is exposed to user Oral cavity and can be used as the first electrode as above.

Fig. 4 F shows an embodiment of iontophoresis device 136, and it is configured to apply To user or the skin of patient.Iontophoresis device 136 include the first electrode 106 " " and Can be used for various iontophoretic application.In another embodiment, whole ion-conductance Ooze therapy instrument 136 be conduction and for electrode.

In one embodiment, the oral cavity (tooth) of user is due to the first positive electrode 106 It is under positive voltage, and the second electrode 108 of brush 126 is under negative voltage with towards positively charged Tooth guides fluorine anion stream.Laboratory experiment illustrates, the flowing of fluorine ion directly depends on and delivered The level of micro-electric current, and higher electric current would be beneficial for delivering in a larger amount fluorine ion and potential Ground is of value to biomembrane and ruptures.Experiment also indicates that, the chopping ion of 80 μ A (amplitude) or less Electric current provides oral care benefits effect hardly.But, higher levels of current may result in user Produce unpleasant sensation, such as electrical sensation, pain and/or tart flavour.Enforcement as herein described Example makes it possible for higher gas current, and does not produce the unpleasant sensation being associated, and And therefore the oral care efficacy of enhancing can be provided.

It is surprising that it has been found by the present inventors that can be in the following way by higher ion-conductance Flow valuve is applied to the oral cavity of user and does not produce unpleasant sensation: at rise time t_RiseIn, Make the micro-electric current of ion from initial current I_InitialRank rise electric current I to terminal_Terminal.In general, when by inciting somebody to action When first electrode 106 is applied to define described circuit in the oral cavity of user, micro-current control circuit 104 produce following micro-electric current I_{Rank liter}, it originates in I_InitialAnd at t_RiseInside it is incremented to I_Terminal, subsequently It is maintained at I_Terminal, until circuit is broken owing to taking out the first electrode 106 from the oral cavity of user Open.When circuit is disconnected and closes, the rank of counterpoise telegram in reply stream rise process every time.As detailed below, Terminal micro-electric current I_TerminalShould be greater than about 100 μ A, micro-electric current of effect is scrubbed in its enhancing being anticipated Value.In one embodiment, terminal micro-electric current I_TerminalBetween about 100 μ A and about 800 μ A. In another embodiment, terminal micro-electric current I_TerminalBetween about 400 μ A and about 800 μ A.Take Certainly in application, micro-electric current I_{Rank liter}Can be alternating current (AC) or DC current (DC).At AC In application, above-mentioned micro-current range is the micro-current value of amplitude.Should be appreciated that aforementioned micro-current range purport Applying for MC, and the nursing application of other non-oral can use different current ranges.

Time t_RiseShould feel to minimize the micro-electric current experienced by user by long enough, but The shortest making rapidly reaches terminal micro-electric current I_TerminalSo that terminal micro-electric current I_TerminalMaximum current Experience by user scrubbing period.The most such as, rise time t_RiseCan be between 1 second And between 20 seconds.In general, rise time t_RiseThe shortest, then user will experience and result from The possibility of the sensation of micro-electric current is the biggest.It should be pointed out that, it may be desirable to the micro-electric current of therapeutic is passed Device 100 is sent to provide certain to feel to user so that user may know that and there is micro-electric current and control The micro-electric current delivery apparatus 100 of the property treated the most correctly operates.But, it should avoid producing unpleasant Micro-electric current of sensation and the rise time.In one embodiment, therapeutic micro-electric current delivery apparatus 100 can be programmed by user so that user may select variable such as rise time t_Rise, initial electricity Stream I_Initial, terminal electric current I_Terminal, stair step current I_Stepping(micro-electric current of the increase between incremental change Amount), frequency, dutycycle etc..

Referring now to Fig. 5 A, it is shown that a DC embodiment (duty of the waveform that micro-electric current rank rise Ratio is equal to 100%).Depict four exemplary micro-current impulse strings 210,220,230 and 240. Should be appreciated that the figure of provided Fig. 5 A-5C is merely for illustrative purposes.Each micro-electric current Train of pulse originates in contact (such as, the micro-current impulse string between the first electrode and the oral cavity of user The contact site 211,221,231 and 241 of the difference of 210,22,230 and 240).In each contact Point, micro-electric current I that rank rise_{Rank liter}Originate in initial micro-electric current I_Initial.Initial micro-electric current I_InitialCan be known Do not make the sensigenous current value of user.As a non-limitative example, initial micro-electric current I_Initial Can be 80 μ A.Micro-electric current I that rank rise_{Rank liter}Subsequently by stair step current I_SteppingIt is incremented by, until when rising Between t_RiseReach terminal electric current I afterwards_Terminal.For clarity sake, phrase " micro-electric current I that rank rise_{Rank liter}” Refer to be applied to all constituents of micro-electric current of user, be included in rise time t_RisePeriod executes Micro-electric current of adding and at rise time t_RiseAfter-applied micro-electric current.Described incremental step frequency Depend on rise time t_RiseWith terminal electric current I_Terminal.The most such as, stair step current I_SteppingCan Equal to about 80 μ A.

In one embodiment, micro-electric current I that rank rise_{Rank liter}I can not be pressed_SteppingIt is incremented by, but as continuously Time signal and the stepping of discrete increase linearly.

At rise time t_RiseAfterwards, at point 212 (with point 232) place, micro-electric current I that rank rise_{Rank liter} It is maintained at terminal current value I_Terminal, until circuit is disconnected (such as, is putting 213,223,233 Hes At 243).In some cases, it can be possible to do not reach terminal current value I_Terminal, because user is upper Rise time t_RiseThe most just it is disconnected circuit, as shown in micro-current impulse string 220 and 240.

Fig. 5 B shows an AC embodiment of micro-electric current rank lifting method.Operation shown in Fig. 5 B Dutycycle is 50%.But, AC embodiment can have be not 50% operation dutycycle.Such as, In one embodiment, dutycycle about can change (the micro-electric current of DC) between 10% and 100%. The rank of pulse rise micro-electric current I_{Rank liter}Frequency can be depending on application-specific.In one embodiment, pulse Rank rise micro-electric current I_{Rank liter}Frequency be about 9kHz.Other frequencies can be utilized.

One complete micro-current impulse string 310 and part micro-current impulse string 320 are illustrated in Fig. 5 B In.About as described in the embodiment shown in Fig. 5 A, when between the first electrode and the oral cavity of user When (such as, at point 311 and point 321) makes electrical contact with, micro-electric current originates in initial micro-electric current I_Initial.At first make contact, micro-electric current is at I_InitialAnd zero alternation between μ A.Micro-electric current i shifts one Side-play amount I_SteppingSo that it is at I_SteppingAnd I_InitialPlus I_SteppingBetween alternation.Micro-electric current presses I further_SteppingDisplacement, until reaching terminal micro-electric current I_Terminal.As time goes on micro-electric current I that rank rise_{Rank liter} Value be represented by operating dutycycle (such as, 50%) at (0+ (m-1) I_Stepping) and (I_Rise _Begin+(m-1)I_SteppingAlternation between), the wherein m=1 when completing circuit, and pass with step frequency Increase one, until (I_Initial+(m-1)I_Stepping)=I_Terminal.At rise time t_RiseAfterwards, what rank rose is micro- Electric current I_{Rank liter}Subsequently with operating frequency at I_Terminal(I_Terminal-I_InitialAlternation between), until circuit is broken Open.

Step frequency depends on rise time t_RiseWith terminal electric current I_Terminal.The most such as, rise Beginning electric current I_InitialWith stair step current I_SteppingCan be 80 μ A.

Fig. 5 C shows another AC embodiment of micro-electric current rank lifting method.Behaviour shown in Fig. 5 C It is 50% as dutycycle.As explained above with described in Fig. 5 B, it is not 50% that AC embodiment can have Operation dutycycle, and the rank micro-electric current I of liter of pulse_{Rank liter}Frequency can be depending on application-specific.One In individual embodiment, the rank of pulse rise micro-electric current I_{Rank liter}Frequency be about 9kHz.

One complete micro-current impulse string 410 and part micro-current impulse string 420 are illustrated in Fig. 5 C In.About as described in the embodiment shown in Fig. 5 A and 5B, when the mouth at the first electrode and user When (such as, at point 411 and point 421) making electrical contact with between chamber, micro-electric current originates in initial Micro-electric current I_Initial.At first make contact, micro-electric current is at I_InitialAnd 0 alternation between μ A.It is micro-that rank rise Electric current I_{Rank liter}Shift side-play amount I_SteppingSo that it is at 0 μ A and I_InitialPlus I_SteppingBetween alternation. Micro-electric current presses I further_SteppingDisplacement, until reaching terminal micro-electric current I_Terminal.As time goes on Micro-electric current I that rank rise_{Rank liter}Value may be expressed as operating dutycycle (such as, 50%) 0 and (I_Initial+(m-1)I_SteppingAlternation between), the wherein m=1 when completing circuit, and with step frequency It is incremented by one, until (I_Initial+(m-1)I_Stepping).At rise time t_{After rising}, micro-electric current of rank liter I_{Rank liter}Subsequently with operating frequency at I_TerminalAnd alternation between 0, until circuit is disconnected.

Fig. 5 D shows another AC embodiment of micro-electric current rank lifting method, and wherein said pulse exists Alternation between the micro-current value of positive and negative, rather than at the most micro-current value and earth potential (that is, zero micro-electric current) Between switch.When between the first electrode and the oral cavity of user (such as, at the point of train of pulse 520 511 and point 521 at) when making electrical contact with, micro-current impulse string 510 originates in initial micro-electric current+I_Initial.In the first contact position, micro-electric current is at+I_InitialWith-I_InitialBetween alternation.So, micro-electric current is just And bear alternation between micro-current value.Micro-electric current I that rank rise_{Rank liter}Equal shift offsets amount on positive and negative direction I_SteppingSo that it is at (-I_Initial-I_Stepping) and (I_Initial+I_SteppingAlternation between).Micro-electric current is further By ± I_SteppingDisplacement, until reaching terminal micro-electric current I_Terminal.As time goes on micro-electricity that rank rise Stream I_{Rank liter}Value may be expressed as operating dutycycle (such as, 50%) at-I_Initial-(m-1)I_Step _Enter) and (I_Initial+(m-1)I_SteppingAlternation between), the wherein m=1 when completing circuit, and with Step frequency is incremented by one, until (I_Initial+(m-1)I_Stepping)=I_Terminal(-I_Initial-(m-1)_Step _Enter)=-I_Terminal.At rise time t_RiseAfterwards, micro-electric current I that rank rise_{Rank liter}Exist with operating frequency subsequently +I_TerminalWith-I_TerminalBetween alternation, until circuit is disconnected.

Fig. 5 E shows another AC embodiment, wherein said pulse the micro-current value of positive and negative it Between alternation.When between the first electrode and the oral cavity of user (such as, at the point of train of pulse 620 611 and point 621 at) when making electrical contact with, micro-current impulse string 610 originates in initial micro-electric current+I_Initial.At first make contact, micro-electric current is at+I_InitialWith-I_refBetween alternation.I_refMay be less than 0 μ A's Any micro-current value.In one embodiment ,-I_refEqual to-I_Initial.So, micro-electric current is at positive and negative Alternation between micro-current value.Micro-electric current I that rank rise_{Rank liter}Shift offsets amount I on the most micro-sense of current_Step _EnterSo that it is at-I_ref) and (I_Initial+I_SteppingAlternation between).Micro-electric current presses I further_SteppingMove Position, until reaching terminal micro-electric current I_Terminal.As time goes on micro-electric current I that rank rise_{Rank liter}Value May be expressed as operating dutycycle (such as, 50%) at-I_ref) and (I_Initial+(m-1)I_Stepping) Between alternation, the wherein m=1 when completing circuit, and be incremented by one with step frequency, until (I_Rise _Begin+(m-1)I_Stepping)=I_Terminal.At rise time t_RiseAfterwards, micro-electric current I that rank rise_{Rank liter}Subsequently with Operating frequency is at-I_refAnd I_TerminalBetween alternation, until circuit is disconnected.

Carry out a research and evaluate and test micro-electric current I that the rank being applied to experimenter are risen_{Rank liter}Sensation Tolerance, by itself and between the first electrode (brush) and the oral cavity of experimenter occur electrical contact time not Micro-electric current that rank rise compares.In the Part I of this research, experimenter uses with 9kHz Micro-electric current I with the 400 μ A AC non-rank liters that 50% operation dutycycle is run_{Non-rank liter}Scrub their tooth Tooth 120 seconds.By the Part I of this research and the Part II of this research, Part III and the 4th Divide and compare, the rank that described Part II, Part III and Part IV are painted according to Fig. 5 C Lifting method provides micro-electric current I that rank rise_{Rank liter}, micro-electric current that described rank rise is respectively provided with 400 μ A, 600 μ A and the I of 800 μ A_TerminalElectric current.Incremental stepping time (the t used of micro-electric current_Stepping) it is 15 Second, and stair step current I_SteppingIt is 100 μ A.Rise time t_RiseIt is 60 for the 400 micro-electric currents of μ A Second, it is 90 seconds for the 600 micro-electric currents of μ A, and is 120 seconds for the 800 micro-electric currents of μ A.

Require that participant presses " stopping " button when they experience unpleasant sensation.? When pressing " stopping " button, the applying of micro-electric current stops immediately, and this event under software records. During this test, experience micro-electric current I that non-rank rise_{Non-rank liter}Experimenter in 55.6% experience Once stop.But, during this test, experience micro-electric current that described various rank rise In the experimenter of (that is, 400 μ A, 600 μ A and 800 μ A), nobody lives through stopping.It addition, Have during micro-testing current that non-rank rise and to stop record and to have also assisted in micro-testing current that rank rise In experimenter, nobody has stopping record during rank rise test.

Also voltage drop in oral cavity is measured, and micro-electric current that micro-electric current of rising for non-rank and rank rise (within the period of 60 seconds, increasing to 400 μ A with the incremental change of 100 μ A from 100 μ A), DC and The micro-electric current of AC and anode and negative electrode polarity compare.In order to determine voltage drop in oral cavity, Measure the potential drop between brush and oral cavity.Relatively low voltage drop is desired, because may be Saliva/tooth powder mixture occurs electrochemical reaction.Fig. 6 A shows the sun with 100% dutycycle Pole result, Fig. 6 B shows the anode result with 50% dutycycle, and Fig. 6 C shows have The negative electrode result of 100% dutycycle, and Fig. 6 D shows the negative electrode result with 50% dutycycle.

It is surprising that be illustrated in graphically in Fig. 6 A-6D these results indicate that In the case of every kind, rise micro-current methods (V with non-rank_{Non-rank liter}) compare, rank rise micro-current methods and produce Relatively low voltage drop (V_{Rank liter}).Rank rise the voltage drop of micro-current methods and almost press factor 2 less than non-rank Rise micro-current methods.This is all real for two kinds of polarity and different dutycycles.Micro-electricity is risen by rank The voltage drop that the less user that stream method provides is relatively low in feeling to be attributable to oral cavity.Therefore, make The micro-electric current I risen with rank_{Rank liter}Make therapeutic micro-electric current delivery apparatus 100 can be with more than 100 μ A Levels of current deliver gas current, and feeling of user is minimum.Micro-electric current due to described increase The reason of level, uses the gas current more than 100 μ A and can provide more preferable oral care efficacy.

Although describing therapeutic micro-electric current delivery apparatus 100 in conjunction with oral care appliance such as toothbrush Rise micro-current methods with the rank being associated, but embodiment is not limited to these.Such as, there is many can Utilize embodiment as herein described is not the MC application of toothbrush.The most such as, rank The micro-electric current risen can be used for increasing micro-electric current in dentistry ionotherapy is applied, and such as treats dentine Super quick (2%NaF), bleb labilais (iodoxuridine), canker sore (methylprednisolone fourth two Acid sodium), anesthesia (injection before local lidocaine) and tooth whitening (hypochlorite), with And other aspects.

It addition, embodiment as herein described can be additionally used in the application outside dentistry ionotherapy. It should be pointed out that, above-mentioned micro-electric current (such as, between 100 μ A and 1000 μ A) is in dentistry Can differ with in the application outside MC.Such as, the first electrode and skin contact wherein In ionotherapy application, gas current level can be more than above for the first electrode and mouth on ten times of ground The micro-electric current of those ions described in contact between chamber.Rank rise micro-electric current other parameters dentistry it Outer application can differ, such as operate dutycycle, frequency, AC or DC electric current etc..Medical science In iontophoretic non-limitative example (wherein can apply the rank liter of embodiment as herein described Micro-current technique) include treating the inflammation in joint and arthritis (corticosteroid), skin analgesia (lidocaine, adrenaline), arthritis (hyaluronidase, vasodilator, citrate / acetate), anoxic ulcer (zinc), tinea pedis (copper sulphate), wart (salicylate) and promise Exhibition scar tissue (iodine).Embodiment can also be used for aesthetic nursing application, and the most micro-electric current is used for making skin Skin is smooth, remove spot, remove wrinkle etc..The ability increasing the micro-magnitude of current being delivered to user can Improve effect of many foregoing ion electric osmose therapy application.

Comparative study-treatment dental plaque

Carried out a research to evaluate and test in toothbrush gas current (electric current of 80 μ A is provided) to controlling Treat dental plaque and the effect of oral malodor.This research is that a kind of single center, single are scrubbed, controlled for four times Treatment, randomization, the crossing research in eight cycles.Register 20 Adult human subjects.This research by Adaptability accesses and eight cycles (cycle 1-8) composition subsequently.Use digital dental plaque imaging analysis (DPIA) dental plaque coverage rate is measured.The purpose of this research is intended to the gas current determining in toothbrush To the effect delivering cetylpyridinium chloride (CPC).

In adaptability during the visit, issue experimenter's adaptability toothbrush (Ionic Handle EW 1045 toothbrush), manual toothbrush and adaptability toothpaste (Cavity Protection tooth powder (0.243% sodium fluoride)).Experimenter scrubs their tooth two minutes in research place, has people The first time supervising them scrubs.Experimenter uses their adaptive product to lead to replace them subsequently The toothbrush often used, uses two to three days altogether, changes described manual toothbrush subsequently into, but the cycle 1 it Before be continuing with adaptability toothpaste 48 hours.

During the cycle 1 to 8, experimenter uses manual toothbrush and adaptation between each research accesses Property toothpaste.Experimenter avoided all of oral hygiene procedures before their upper once designated time Within 12 hours, (their scrub for the last time is to be accessed the evening before day arrange (7:00pm)).Experimenter before their upper once designated time also avoid feed, drinking-water, Chew gum and smoking (including smokeless tobacco) four hours.Only allow to drink the water of osculum, Do not want Xia Shui before measuring in 60 minutes next time.

During the cycle 1 to 7, each experimenter is randomly assigned one of four treatments, and described four Secondary treatment is as follows:

Treatment A: use 20ml water rinse 30 seconds, uses subsequently and has double ion brushIonic Handle EW-DE-40 test toothbrush (is connected sound, is connected 80 μ A ion (anode) electric currents) and adaptability toothpaste carry out two minutes scrub；

Treatment B: use 20ml water rinse 30 seconds, uses subsequently and has double ion brushIonic Handle EW-1045 test toothbrush (connect sound, connect from Electron current) and adaptability toothpaste carry out two minutes scrub；

Treatment C: by solution (comprising the 5ml CPC being dissolved in 20ml water) rinse 30 seconds, Use subsequently and there is double ion brushIonic Handle EW-DE-40 is real Test toothbrush (connecting sound, connect 80 μ A ion (anode) electric currents) and adaptability tooth Cream carries out two minutes scrub；With

Treatment D: by solution (comprising the 5ml CPC being dissolved in 20ml water) rinse 30 seconds, Use subsequently and there is double ion brushIonic Handle EW-1045 is real Test toothbrush (connecting sound, connect gas current) and adaptability toothpaste carries out two minutes Scrub.

Experimenter is supervised when carrying out the oral hygiene order of above-mentioned distribution, and in the afternoon Imaging experiment room is returned to carry out imaging between 2:00 and 3:00pm.Experimenter's measurement in the afternoon Avoid feed before and drink water 60 minutes.During imaging, according to following code to each experimenter Shooting DPIA UV image:

By 25ml phosphate buffer rinse 10 seconds；

By the 5.0ml phosphate buffer rinse 1 minute containing 1240ppm fluorescein；

By 25ml phosphate buffer rinse 3 times, each 10 seconds；And

Obtain DPIA UV image.

The camera chain being used for shooting DPIA UV image includes high-resolution digital camera, its Eyeglass and double permission of linear polarization with 25mm produce crossed polarized light.UV flash lamp provides Illumination.Described camera is connected to personal computer, and described computer recording also analyzes image.Catch Maxilla and the digital picture on mandibular front face surface are obtained.To tooth and dental plaque in digital picture Pixel is classified, and calculates the dental plaque percentage of coverage to tooth.For ease of checking, inspection Looking into the illumination in room is ambient lighting.Experimenter is sitting in the stool being used for fixing before the chin torr of head On.Plastics retractor is used to make its lip and cheek retraction.The incisal edges of front tooth is put together And it is the most placed in the middle.Before exposure, experimenter determines by its tooth air-breathing and by its tongue Position becomes to make tongue invisible away from tooth.

During the cycle 8, experimenter is randomly assigned certain treatment order as above.It is subject to Examination person returns to imaging experiment room between 2:00 and 3:00pm, and avoided before image measurement into Eat and drink water 60 minutes.During the imaging in cycle 8, according to following code, each experimenter is clapped Take the photograph DPIA UV image:

By 25ml phosphate buffer rinse 10 seconds；

By the 5.0ml phosphate buffer rinse 1 minute containing 1240ppm fluorescein；

By 25ml phosphate buffer rinse 3 times, each 10 seconds；And

Obtain DPIA UV image.

For each experimenter in each treatment cycle, produce average percent dental plaque coverage rate. Using the variance analysis for cross-over design to analyze dental plaque percentage, described cross-over design is in a model Have expression experimenter (random effect), cycle, carry, rinse (water/hexadecyl pyrrole Pyridine) and the factor of ion power (on/off).It is also carried out between described 4 therapeutic schemes All paired comparisons.

Result

Fig. 7 for dental plaque change (AP) figure that compares, the change of described dental plaque result from without from Water rinse during electron current (is labeled as " H₂0,0 μ A "), without the chlorination 16 during gas current Alkyl pyridine (CPC) rinse (being labeled as " CPC, 0 μ A "), when having an anode ion electric current CPC rinse (being labeled as " CPC, 80 μ A, A ") and CPC when having cathode ion electric current Rinse (is labeled as " CPC, 80 μ A, C ").The CPC rinse effect in time without gas current exists The relative dental plaque being about 5% under the conditions of described reduces the (dental plaque coverage rate (p-0.2 of about-0.64 unit To water).

Anode ion electric current should make oral tape negative electricity, thus drives more CPC to enter in theory Enter in tooth.The figure of Fig. 9 shows, and compared with CPC rinse during gas current, and anode Gas current with increments improve dental plaque reduce-from about-0.64 to about-0.98 unit (p ＜ 0.5 is right Water；P-0.2 is to CPC tester).But, cathode ion electric current result on the opposite way round Dental plaque reduces, and this makes the efficiency efficiency less than individually washing of CPC rinse.

Accordingly, it is shown that, when combining CPC rinse scheme and using, 80 μ A anode ion electric currents can Some beneficial effects are provided.

Comparative study-oral malodor

Carried out oral malodor research, it include single center, three treatments, randomization, three The cross-over design in cycle.Register at most 20 Adult human subjects.In general, this research is every Individual treatment cycle by the adaptability/flushing cycle of at most three days before the 1st of this research the day, five days The research duration composition, wherein halitosis instrument (implication) measure at the 2nd day, the 3rd day and the 5th It is carried out, and tongue and oral cavity is washed the micro-sampling washed collection in the 1st day and the 5th day.Experimenter The treatment product using Random assignment completes three treatment cycle.

Halitosis instrument unit testing to volatile sulfur compounds (VSC).Described halitosis instrument is to stench Two kinds of i.e. hydrogen sulfide of key component and methyl mercaptan in implication are sensitive.Professional and technical personnel implements all of Halitosis instrument measures.It is as follows that code measured by described halitosis instrument: instruction experimenter keeps their oral cavity to close Two minutes.A piece of barrier tape is placed on halitosis instrument plate and (is placed on the upper of hole by experimenter subsequently Side), then by a paper cylinder (about 1.75 inches of long diameters taking advantage of 1 1/16 inches) cleaned One end through the hole in halitosis instrument plate.Experimenter is instructed to swallow before their halitosis instrument is measured (if they are ready) 30-45 second, it is ensured that their oral cavity remains closed.Two minutes it After, indicate experimenter's nose by them and hold their breathing.Technical staff is tested Person will record background halitosis instrument value before halitosis instrument.Experimenter have subsequent access to halitosis instrument, and By their tooth and lip loosely around described pipe while the breathing holding them.Tested During person holds their breathing, this instrument bleeds (oral cavity not contacting experimenter) from oral cavity, And technical staff records measured value indicated on this instrument.Then experimenter to remove them used Barrier tape and paper cylinder and they are discarded in suitable container.

During the adaptability cycle, issuing experimenter's adaptive product, described product is by ADA benchmark Manual toothbrush andCavity Protection (4.6oz) tooth powder (being contained in pipe) composition.It is subject to Examination person scrubs their tooth with their adaptive product, twice daily, is continued up to three days.

In this research whole, instruct the food of experimenter's not edible height seasoning or dislike with oral cavity The smelly food (such as, garlic) being associated, and during the adaptability cycle and each treatment cycle The most not drinking of period.Experimenter also will be in their upper access once arranged The night carrying out them evening before 11:00pm before (the 1st day) scrubs, and to avoid Any kind of oral hygiene and breath mints, pastille lozenge, take food, drinking water (only allows little Mouthful water, upper once measure before do not drink water 45 minutes), in their upper once designated time Smoking after their night scrubs in evening before, chew gum or chewing tobacco.

1st day

Issuing experimenter and comprise the treatment kit for the treatment of product, described treatment product includes that one is controlled Treatment toothbrush (Twin Ionic " AySy " brush holder EW-DE-40 (anode),Twin Ionic " CySy " brush holder EW-DE-40 (negative electrode) or Ion shank EW 1045 brush holder),Cavity Protection (4.6oz) tooth powder and Metback double ion brush.Described Metback double ion brush brush dorsal surface (that is, with There is the head surface that the side of bristle is relative) on there is conductive surface.It addition, described Metback Double ion brush also have be positioned at the first electrode below bristle and be positioned at bristle directly below Second electrode.

Treatment based on Random assignment order distributes treatment kit.Experimenter was the treatment of five days Identical treatment product is used in cycle (Monday is to Friday).

Microorganism tongue sample is obtained as follows: new by one lightly from each experimenter , the toothbrush of cleaning be placed on tongue at right one side of something or left one side of something of center line, light on tongue surface Micro-ground agitation bristles five seconds.From the right side of tongue, still left side is collected whole panelist In carry out at random.This toothbrush is transferred to bottle subsequently, and described bottle comprises 10mL microorganism Transmission fluid (reduced form transmission fluid (RTF)), and brush is sterilely clipped to bottle In.Subsequently bottle sealed and be maintained on ice, until being plated on microbiological culture media.Receive subsequently Collect micro-oral cavity to wash and wash sample.Experimenter is instructed effectively to rinse their mouth with 10mL aseptic USP water 30 seconds, chamber, and spat in collecting pipe.By the seal of tube and be stored on ice, until plating On microbiological culture media.The 1st day and the 5th day collection micro-biological samples in each treatment cycle. Test tongue and oral cavity wash the micro-sample washed Gram-negative bacteria anaerobe (GNA), Total amphimicrobe (TNA) and the producer of sulphur.

Experimenter is instructed to scrub with treatment product in the following way: as instruct, often It is scrubbed their tooth for twice and cleans their tongue.Scrubbing for tooth, following guidance is tested Person:

It is attached brush securely；

Grasping main body, catch tactile ion panel；

Wetting brush also applies enough toothpaste to cover brush；

Select a kind of " pattern " (first mode " strongly ")；

Before connecting toothbrush, sprawl toothpaste around tooth compactly；

In order to avoid sputtering, making operation switch time at brush in the oral cavity；

Move brush with circular motion slightly, be similar to manual toothbrush；

After a few seconds, bristle is guided to next part；

Terminate after one minute to scrub；

When completing to scrub, switched by push and turn off toothbrush；

Unnecessary toothpaste is told in basin.

By rinse in the oral cavity 10ml water within 10 seconds, come rinse fall remnants toothpaste；And

Tell in basin.

Tongue is scrubbed, instructs experimenter as follows:

The dorsal surface of brush is disposed initially at tongue from rear portion and switches on power.By tongue portion Become 2 parts (left side of tongue center line and the right).From the beginning of rear left side, use circumference Move on the left of tongue and clean tongue 30 seconds.Right side is repeated to 30 seconds added. Power cutoff.

Any additional toothpaste saliva is told in basin.

Within 10 seconds, final rinse is carried out by rinsing with 10ml water.

Rearrange and require that experimenter returns for two hours after they carried out the time scrubbed.This Outward, also remind experimenter, after their two hours scrub, avoid any kind of oral cavity before agreement Health and feed, drinking-water, smoking or use breath mints, pastille lozenge, chewing gum or chew Tobacco.Obtaining micro-sample of two hours subsequently, according to randomization chart, sample is from tongue center line Opposite side obtains, and the most have collected sample from described opposite side with same way described above. The most also wash with same way described above collection oral cavity and wash sample.

Described treatment product is placed on described place (being stored in kit) and instructs experimenter Their adaptive product it is continuing with during scrubbing night.

2nd day

Experimenter returns to described place with their adaptability kit.Carry out baseline (BL) mouth Smelly instrument implication is measured, and carries out subsequently: 1) standardization breakfast (bagel, cream cheese and water)； 2) treatment kit is redistributed；3) explanation is scrubbed in review；With 4) supervision treatment product carries out The scrubbing and scrape tongue of tooth.

Rearrange and require that experimenter returns for three hours after they carried out the time scrubbed. The halitosis instrument implication carried out three hours is measured.Instruct experimenter's evening before their access in the 3rd day On carried out scrubbing in their night before 11:00pm.

3rd day

In the morning accessed at the 3rd day, experimenter returns test site, does not carry out any type Oral hygiene and not feed, drinking-water or smoking, as mentioned above.Last experimenter After the measurement of BL implication about 24 hours, carry out 24 hours halitosis instrument implications and measure, be followed by mark Standardization breakfast, the tooth carrying out being subjected to supervision with treatment product are scrubbed and scrape tongue, as mentioned above.

Rearrange experimenter's three hours return checkout areas after the tooth scrubbing them and tongue Institute.The halitosis instrument implication carried out 27 hours is measured.

Experimenter is instructed to follow identical brushing regimen at home: with treating product brushing teeth and scraping Tongue, twice daily (morning and evening).This research access before last (be not subjected to supervision ) scrub night and continue to carry out before 11:00pm.

Rearrange and remind the food or relevant to oral malodor of experimenter's not edible height seasoning Connection food, do not drink.

4th day

Experimenter is continuing with their treatment product (morning and evening at home as instruct Use).

5th day

At the 5th day, experimenter returned with their treatment kit, and carries out implication measurement Acquisition with micro-sample.Experimenter evening before their access arranged is at 11:00pm Scrubbed their tooth with treatment product before.

Experimenter accepts halitosis instrument implication and measures, and is followed by the collection of micro-sample (according to aforementioned rule Journey).Experimenter returns their treatment product, and redistribute flushed kit for Flushing between each treatment cycle.Rearrange the 1st day for the treatment of cycle next time of experimenter, and And remind them i.e. on one to the Friday of phase with the week that research accesses during each treatment cycle The food of the most not edible height seasoning or the food that is associated with oral malodor (i.e., greatly Garlic) and do not drink.Additionally, also remind experimenter in their upper access once arranged The night carrying out them evening before 11:00pm before (the 1st day) scrubs, and at them Designated time next time before evening after their night scrubs, to avoid any kind of mouth Chamber health and feed, drinking-water, smoking or use breath mints, pastille lozenge, chewing gum or nozzle Chewing tobacco.

Have collected tongue and oral cavity is washed after washing sample, hold them in 4 DEG C, until by by The microbiology personnel of training carry out process (4 hours after collection of specimens on the same day to them In).For each each experimenter every in three sample time point, determine and report from (BL 2 hours, treated after treatment in the 1st day the estimated value of the bacterium that sample reclaims with the 5th day Afterwards).

Analyze

Before any statistical analysis, the volatilization measured by halitosis instrument with natural logrithm Scaling Analysis Property sulphur compound.Average result is converted back into initial scale.The covariance for crossing research is used to divide It is poor to determine treatment that analysis (ANCOVA) analyzes (24 hours point) halitosis instrument overnight data Not.Described ANCOVA model include experimenter's (at random), the cycle, treatment and (if institute State the conspicuousness that 10% level has in statistical significance) carry, wherein by (the 2nd day) baseline halitosis Instrument score value is as covariant.

Measure for after each baseline, analyze data independently.Use covariance as above After other baselines of analytical, score value (3 hours, 27 hours and the 5th day) is to determine treatment Difference.

Determine in described three single culture mediums each on the described Log10 of organism that reclaims The estimated value that colony forming single-digit (CFU) converts, and report often for each treatment cycle The individual experimenter each feelings in described three sub-sampling time points (baseline, 2 hours and the 5th day) Condition.Above-mentioned similar ANCOVA method is used to have evaluated described 2 hours of the 1st day independently micro- Micro-sample of sample and the 5th day, to determine treatment difference, wherein uses the baseline sample conduct of the 1st day Covariant.Start additionally, use paired t-test to test zero also for each toothbrush from baseline The minimizing of the 5th day reducing and starting from baseline for described 2 hours.Statistical check to result for the treatment of is Two-sided test, is carried out with 5% significance.

Result

VSC halitosis instrument result and the tongue sample GNA bacterium result of the 5th day of this research are shown respectively In Fig. 8 and 9.The vertical axis of Fig. 8 institute diagram is the parts per billion (ppb) that measured the 5th day obtains (ppb) volatile sulfur compounds content.The vertical axis of Fig. 9 institute diagram is the 5th day tongue obtained On log GNA bacterium.In figs. 8 and 9, for nonionic electric current therapy result trunnion axis mark Being designated as 0 μ A, results of weak current micro-for anode is labeled as 80 μ A, A, and electric current micro-for negative electrode Result queue is 80 μ A, C.

As shown in Figure 8, compared with zero micro-electric current therapy, the micro-electric current of anode 80 μ A provides oral cavity and dislikes Smelly slight decrease, and the described 80 micro-electric currents of μ A provide significantly reducing of oral malodor.Similar Ground, as it is shown in figure 9, the micro-electric current of anode 80 μ A and zero micro-electric current therapy are compared, to provide GNA thin Bacterium reduces, and the micro-electric current therapy of negative electrode 80 μ A provides compared with the anode 80 micro-electric current therapy of μ A GNA bacterium reduces.

It is therefore intended that the electric current that local applies can produce antibacterial benefit, described antibacterial useful effect Fruit is converted into clinical efficacy.

The gas current research that rank rise

Carried out a research, with evaluation and test use rank rise micro-current control method time more than 80 μ A Micro-electric current to reducing dental plaque and the effect of oral malodor.This research be single center, three times treatment, Randomized, the cross-over design in three cycles.In this study, register at most 20 tested Person.In general, the adaptability cycle of about 3 days before this research includes the cycle 1.This intersection (Monday was to week for lasting five days for each in described three treatment cycle of research and design Five).During each treatment cycle, experimenter produces with their test at test site under supervision Product scrub their tooth, twice daily.They stay at home the most once a day (at night) use them Adaptive product scrub.In addition to the afternoon of the 5th day, capture three DPIA figures every day As (morning before scrubbing and after scrubbing and scrub afternoon before).Exist between each treatment cycle The flushing in a few week.Repeat this research method, until experimenter uses controlling of their Random assignment Treatment scheme completes three treatment cycle.

Adaptive product is provided to the experimenter showing dental plaque evidence (based on method for sieving) Adaptability kit, described adaptive product includes two ADA benchmark manual toothbrush and two pipesCavity Protection (4.6oz) tooth powder (is contained in pipe).Adaptability used as described below is produced Product: 1) during adaptability cycle before the cycle 1；2) during treatment cycle, it is used as theirs Night scrubs product；And 3) be used as to rinse product between each treatment cycle.For adaptability/ Flushing cycle, instructs experimenter to use their adaptive product to replace their conventionally used tooth Cream and toothbrush carry out scrubbing (in their common mode), twice daily.Experimenter protects at home Hold their adaptive product, until their final cycle 3, within the 5th day, access.

In this research whole, place staff is by phone or tested by reminding e-mail Person carries out scrubbing the evening before their cycle 1 accesses before 11:00pm night, and in institute Avoid carrying out any oral hygiene in the morning stating access.Additionally, place staff also reminds experimenter Do not take food after completing to scrub night, drink water, smoking, use breath mints, containing lozenge Agent (such as, cough or throat drops) and chewing gum.When carrying out the studies above, inform tested The water of person's osculum is to allow, but they should avoid drinking-water before accessing in 45 minutes.

Tooth paste product for this research is the Crest Pro-Health toothpaste improved.As improving shape Formula, FDC blue color component and all flavor ingredients all save from tooth powder.

1st day, morning

Experimenter returned after avoiding all oral hygiene procedures in the morning of their designated time Described place.Obtain DPIA and scrub front image morning.

Measuring for DPIA, experimenter exposes dental plaque, and (that follows above for described in comparative study is glimmering Light element dental plaque process for exposing) and (use is as mentioned above to shoot their the front digital picture of scrubbing of labial teeth UV imaging system).

It is randomly assigned treatment order to experimenter.The distribution for the treatment of order is only carried out in the cycle 1. Experimenter uses identical treatment product in the treatment cycle (Monday is to Friday) of 5 days.Institute State treatment product to includeTwin Ionic EW-DE-40-01 brush holder (depends on treating suitable Sequence, no current, anode current or cathode current) and there is the brush of conductive filament.Brush Filament is nylon filament, they have the conductive core composite of carbon (nylon with) and non-conductive outside Shell.

The electric current applied is zero current (treatment order A), the just micro-electric current of (anode) square wave (treatment order B) or the negative micro-electric current of (negative electrode) square wave (treatment order C).Applied is micro- Electric current has frequency and the dutycycle of about 80% of about 9kHz.Micro-current amplitude is by rank liter, such as figure Shown in 5C, wherein I_InitialEqual to 80 μ A, I_Stepping25μA.The speed that micro-electric current rises with the rank of 80 μ A/sec Degree is incremented by, until reaching maximum micro-current amplitude (I of about 400 μ A_{Rank liter}).Once reach 400 μ A, micro-current amplitude remains in this platform, until losing electrical contact, as mentioned above.

Treatment access time use before, to experimenter provide treatment scrub explanation (word and mouth Head).Treatment is scrubbed and is described as follows:

With running water rinse oral cavity before scrubbing；

It is attached brush securely；

Grasping main body, catch tactile ion panel；

Brush is soaked with running water；

The Crest Pro-Health toothpaste of improvement is applied on brush；

Wetting will grasp the hand of toothbrush；

Select a kind of " pattern " (first mode " strongly ")；

Brush is placed on the outer surface of upper tooth.Toothbrush bristle should be towards gum line slightly angulation Degree ground is placed against tooth；

Connect toothbrush, and start to scrub with circular motion slightly.Slightly execute scrubbing period Plus-pressure.After a few seconds, bristle is guided to next part.In whole process In, with the identical inner side of motion brushing teeth, outside with chew face；

Scrub each part 30 seconds；

Completed to scrub after two minutes；

When completing to scrub, switched by push and turn off toothbrush；

Tell in basin.

Experimenter scrubs with treatment product, as instruct, scrubs theirs twice daily Tooth (morning and afternoon, be subjected to supervision onsite application).After scrubbing, experimenter uses fluorescein weight Newly expose their dental plaque, and shooting is scrubbed DPIA image in rear morning.

Experimenter returns to described place to carry out the access in afternoon.Experimenter exposes dental plaque, and Shoot the DPIA image in afternoon before their labial teeth is scrubbed.Then, the toothbrush of experimenter's distribution is followed Their tooth and tongue is scrubbed in the explanation in morning.Experimenter brushes at night with adaptive product at home Wash their tooth.

2nd day-4, morning

Experimenter returns to described place in the morning and exposes their dental plaque and (follow fluorescein dental plaque sudden and violent Dew method), and shoot their labial teeth scrub front DPIA image.Then, experimenter follows Explanation their tooth of cleaning of 1 day.After scrubbing, experimenter exposes them with fluorescein again Dental plaque, and shoot and scrub DPIA image in rear morning.

2nd day-4, afternoon

5th day, morning

Experimenter returns to described place in the morning and exposes their dental plaque and (follow fluorescein dental plaque sudden and violent Dew method), and shoot their labial teeth scrub front DPIA image.Thereafter, experimenter's distribution Treatment product follow the tooth scrubbing them described above and tongue.After scrubbing, experimenter's weight New fluorescein exposes their dental plaque, and shoots and scrub DPIA image in rear morning.

Experimenter is instructed to use their adaptive product in a week (flushing cycle) subsequently, Until their treatment next time accesses.Them are reminded to keep away in the morning of their upper once designated time Exempt from all oral hygiene procedures；This means their scrub in the access day arranged for the last time Evening (earlier than 11pm) before.Additionally, also remind experimenter after completing to scrub night Do not take food, drink water, smoking, use breath mints, pastille lozenge (such as, are coughed or swallow Larynx drops) and chewing gum.Inform that the water of experimenter's osculum allows being, but they should visit Within before asking 45 minutes, avoid drinking-water.

Analyze

Dental plaque suppression in morning (before scrub in the morning).For the 2-5 days, use for cross-over design The analysis of covariance (ANCOVA) analyzes the DPIA in morning of every day independently and scrubs the covering of front dental plaque Rate, to determine treatment difference, has expression experimenter (random effect), cycle in a model, controls The term that treatment and (if 10% level has the conspicuousness in statistical significance) are carried, wherein will Within 1st day, scrub front DPIA to measure as covariant.

Afternoon, dental plaque regrowed (before scrub in the afternoon): for the 1-4 days, uses and sets for intersection The analysis of covariance (ANCOVA) of meter analyzes the DPIA in afternoon of every day independently and scrubs front dental plaque Coverage rate to determine treatment difference, have in a model expression experimenter (random effect), the cycle, The term that treatment and (if 10% level has the conspicuousness in statistical significance) are carried, wherein Scrubbed front DPIA to measure the 1st day as covariant.

Dental plaque reduce (morning scrub before deduct scrub after): for the 1-5 days, be used for intersecting The analysis of covariance (ANCOVA) of design analyzes the most independently before DPIA in morning scrubs and deducts After scrubbing, (reduction) score value is to assess result for the treatment of, has expression experimenter in a model and (imitates at random Really), cycle, treatment and (if 10% level be in statistical significance notable) are carried Term, wherein scrubbed the 1st day front DPIA and measures as covariant.

Duplicate measurements (day effect).It addition, in order to observe the DPIA dental plaque trend across the time, The duplicate measurements ANCOVA for cross-over design is used to analyze following variable independently, at model In have expression experimenter (random effect), cycle, treat, carry (if notable) and The term of time, wherein scrubbed front DPIA as covariant using the 1st day:

(the 2-5 days) before scrubbing morning,

Before scrubbing afternoon (the 1-4 days) and

Dental plaque reduces (deducting before the scrubs for 1-5 days after scrubbing).

Result

It should now be understood that, embodiment as herein described can increase in iontophoretic application Add the micro-levels of current of ion, and not by gradually carrying from initial current electric current to terminal within the rise time High micro-electric current and cause unpleasant sensation to user or patient.In MC is applied, rank The micro-electric current risen reduces the voltage drop in oral cavity, and allows have the electric current water more than 100 μ A Flat.Micro-electric current rank as herein described rise technology can be as any number of iontophoretic application Realize.

Dimension disclosed herein and value are not intended to be understood to be limited strictly to described exact value. On the contrary, except as otherwise noted, each such dimension is intended to indicate that cited value and around this value merit The scope of equivalent can be gone up.Such as, the dimension being disclosed as " 40mm " is intended to indicate that " about 40mm”。

Every document cited herein, including any cross reference or relevant patent or patent Shen Please, the most hereby it is incorporated herein in full with it, unless got rid of or the most limited in plain text.Right Quoting of any document is not to recognize that it is disclosed herein or claimed any Bright prior art or recognize its independently or with any other one or more bibliography appoint This type of invention any is taught, advises or disclosed to the mode of what combination.Additionally, when art in the literature Any implication of language or definition with in the document being incorporated herein by reference same term any implication or During definition conflict, will be as the criterion with the implication or definition that give that term in the literature.

Although illustrate and describe only certain embodiments of the present invention, but those skilled in the art Change it will be appreciated that various other can be made without departing from the spirit and scope of the present invention With the form of correction.Therefore, all these in following claims is intended to the scope of the invention change Become and modification.

Claims

1. a therapeutic micro-electric current delivery apparatus (100), including:

First electrode (106), described first electrode is operable to in the first user position Place makes electrical contact with user；

Second electrode (108), described second electrode is operable to in the second user position Place makes electrical contact with described user；

Power supply (102), described power supply is operable to provide first at described first electrode Electromotive force and provide the second electromotive force at described second electrode；

Micro-current control circuit (104), described micro-current control circuit and described first electrode (106), described second electrode (108) and described power supply (102) electric connection, wherein:

The electrical contact of described first electrode of described first user position and described The electrical contact of described second electrode of two user positions completes at described first electrode And the circuit between described second electrode；And

When completing described circuit, described micro-current control circuit produces by described Micro-electric current I of the user between the first user position and described second user position_{Rank liter}, described micro-electric current is at rise time t_RiseInterior from initial current I_InitialIncrease to terminal Electric current I_Terminal,

It is characterized in that t_RiseBetween 5 seconds and 20 seconds；Described first user position is described The oral cavity of user；And described micro-electric current I_{Rank liter}Produce the Current Voltage fall V that rank rise_{Rank liter}, The Current Voltage fall V that the Current Voltage fall that described rank rise rises less than non-rank_{Non-rank liter}, described non-rank liter Current Voltage fall result from the electric current I that non-rank when completing described circuit rise_{Non-rank liter}。

Therapeutic the most according to claim 1 micro-electric current delivery apparatus, the micro-electricity of wherein said therapeutic Stream delivery apparatus is oral care appliance (120).

Therapeutic the most according to claim 2 micro-electric current delivery apparatus, wherein said terminal electric current I_TerminalMore than 100 μ A.

Therapeutic the most according to claim 2 micro-electric current delivery apparatus, wherein said terminal electric current I_TerminalBetween 100 μ A and 800 μ A.

Therapeutic the most according to claim 2 micro-electric current delivery apparatus, wherein said terminal electric current I_TerminalBetween 400 μ A and 800 μ A.

Therapeutic the most according to claim 1 micro-electric current delivery apparatus, wherein t_RiseBetween 15 seconds And between 20 seconds.

Therapeutic the most according to claim 1 micro-electric current delivery apparatus, wherein t_RiseIt it is 16 seconds.